Molecular and Cellular Oncology Research Program

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PROJECT SUMMARY/ABSTRACT The goal of the Molecular and Cellular Oncology (MCO) Research Program is to gain a comprehensive understanding of basic mechanisms driving cancer initiation, progression, metastasis and therapeutic resistance to facilitate development of novel and rational approaches for cancer prevention and therapy. MCO research efforts are central to the overall Markey Cancer Center (MCC) mission to reduce the cancer burden with a focus on Kentucky and its most vulnerable populations through research, prevention, treatment, education and community engagement. MCO investigators determine signaling, genetic, epigenetic and metabolic mechanisms that promote cancer development, fuel tumor progression and contribute to therapeutic resistance. To achieve its goal, MCO proposes three inter-related aims: 1) Identify aberrant signaling networks and critical interactions of tumor cells with their microenvironment to delineate molecular mechanisms that drive tumor initiation, progression and metastasis and resistance; 2) Determine the contribution of metabolic reprogramming and epigenetic dysregulation to define novel pathways promoting cancer cell survival and adaptation; 3) Delineate the mechanisms by which dysregulation of redox signaling promotes genomic instability, therapeutic resistance and normal tissue toxicity. The 54 members of the MCO Program are experts in cancer cell signaling, tumor microenvironment, cancer metabolism, epigenetic regulation and redox biology who hail from 16 departments in the Colleges of Medicine; Engineering; Arts and Sciences; and Agriculture, Food and Environment, reflecting diverse disciplinary perspectives. Cancer-related MCO funding is nearly $10.3M in annual direct costs, and 53% of MCO peer-reviewed funding is from the NCI. Members have published 320 manuscripts (July 2018–June 2022), of which 106 (33%) are inter-programmatic, 81 (25%) are intra-programmatic, and 195 (61%) are inter-institutional. The program is co-led by three researchers with expertise in each of the three programmatic areas. Dr. Rina Plattner (an expert in oncogenic kinase signaling and tumor metastasis), Dr. Binhua “Peter” Zhou (a specialist in epigenetic and metabolic reprogramming of epithelial-mesenchymal transition) and Dr. Tianyan Gao (an expert in protein phosphatases and mitochondrial regulation of cancer stem cells) bring together expertise in cancer signaling (Plattner, Aim 1), epigenetics and metabolism (Zhou, Aim 2) and redox biology and mitochondrial bioenergetics (Gao, Aim 3). In addition to their scientific leadership, each offers significant strengths in clinical translation, junior faculty mentoring, communications among MCC Research Programs and expertise on populations within the MCC catchment area. By leveraging comprehensive program strengths, the MCO Program collectively provides a rich environment to facilitate multidisciplinary collaboration and builds a productive pipeline for translation of MCO science into the clinic.